Transcriptional corepressor activity of CtBP1 is regulated by ISG15 modification.

C-terminal binding protein 1 (CtBP1) is a critical transcriptional corepressor of many tumor suppressor genes and plays diverse roles in the progression of cancers. The transcriptional repression function of CtBP1 is mediated by recruiting histone-modifying enzymes, such as histone deacetylases and histone methyltransferases, to target genes by binding with DNA-interacting factors. Several post-translational modifications of CtBP1 have been identified, including ubiquitination, phosphorylation, and SUMOylation. This paper reports that CtBP1 is conjugated by ISG15. Endogenous CtBP1 was modified by ISG15 after interferon-α treatment in HeLa cells. The ISGylation process of CtBP1 was regulated by deISGylation enzyme USP18 and ISG15 E3 ligase EFP. Interestingly, CtBP1 ISGylation affected the binding affinity between CtBP1 and some components of CtBP1-associated transcriptional complexes. HDAC1 and LSD1 bound more efficiently to ISG15-conjugated CtBP1 than non-conjugated CtBP1. On the other hand, binding between CtBP1 and HDAC4 was unaffected by ISG15 modification. Furthermore, ISG15 modification enhanced the transcriptional repression activity of CtBP1 on several target genes related to EMT and apoptosis. These findings suggest that the ISG15 modification of CtBP1 modulates the function and activity of CtBP1 and that CtBP1 ISGylation may provide a new insight for CtBP1-mediated cancers.

Association among the Prevalence of Sarcopenia without Obesity, Nonsarcopenic Obesity, Sarcopenic Obesity, and Metabolic Syndrome in Cancer Survivors: Based on Korea National Health and Nutrition Examination Survey.

OBJECTIVE: In this study, we aimed to investigate the association among the prevalence of sarcopenia without obesity, nonsarcopenic obesity, sarcopenic obesity, and metabolic syndrome in cancer survivors using data from the 4th and 6th Korea National Health and Nutrition Examination Survey (KNHANES), a nationally representative data source. METHODS: The 4th and 6th KNHANES was conducted in 2008-2011. Data from cancer survivors were obtained including 133 obese patients without sarcopenia, 98 obese patients with sarcopenia, and 87 patients with sarcopenia but without obesity. SPSS 22.0 was used for statistical analysis with complex sample survey modules and commands. RESULTS: The prevalence of metabolic syndrome was 25.3% in the sarcopenia without obesity group, 61.7% in the nonsarcopenic obesity group, and 67.3% in the sarcopenic obesity group, showing the highest rate in the sarcopenic obesity group, with a significant difference among the three groups (P < 0.001). CONCLUSIONS: In this study, the prevalence of metabolic syndrome was 25.3%, 61.7%, and 67.3% in the sarcopenia without obesity, nonsarcopenic obesity, and sarcopenic obesity groups, respectively, showing that the sarcopenic obesity group had the highest metabolic syndrome rate. Based on these results, various education programs for the prevention and treatment of metabolic syndrome should be developed for cancer patients.

Relations between the blood lead level and metabolic syndrome risk factors.

OBJECTIVE: This study is to examine the relations between the blood lead level, which has an effect on lipid metabolism in the body, and metabolic syndrome to establish a basic reference for the development of a local community health management program. DESIGN AND SAMPLE: This study is a descriptive correlational study about verifying the relation between the blood lead level and metabolic syndrome risk factors. A total of 2,833 respondents' data were sampled on the 1st year (2016) data of the 7th Korea National Health and Nutrition Examination Survey conducted by the Korean Centers for Disease Control and Prevention (CDC). MEASURES: The data were analyzed to explore blood lead level differences by demographic characteristics, correlations between the blood lead level and metabolic syndrome risk factors using chi-square test, Mann-Whitney U-test, Pearson correlation coefficient, and binary logistic regression. RESULTS: Systolic and diastolic blood pressure, triglycerides (TG), and FBS demonstrated a significant difference by blood lead level (p < 0.001). Systolic and diastolic blood pressure, waist circumference, and FBS and TG levels were positively correlated with blood lead level (p < 0.005), whereas high-density lipoprotein cholesterol was negatively correlated (r = -0.038, p < 0.005). CONCLUSION: This study confirmed that the blood lead level was significantly correlated with all metabolic syndrome variables.

Sarcopenia in cancer survivors is associated with increased cardiovascular disease risk.

PURPOSE: The aim of this study was to assess the association between sarcopenia and cardiovascular disease (CVD) risk in cancer survivors. METHODS: We analyzed a consecutive series of 683 cancer survivors from the Korean National Health and Nutritional Exam Survey (2008-2011 years). Sarcopenia was defined as the appendicular skeletal muscle mass divided by weight (Kg) < 1 standard deviation below the sex-specific healthy population aged 20-39 years. CVD risks were assessed using the Framingham Risk Score (FRS), which were divided by tertile. Predictors of higher shift of FRS tertile by sex were calculated by stratified ordinal logistic regression analyses. RESULTS: Proportions of sarcopenia were 24.2% in males and 22.5% in females. Sarcopenic survivors were more likely to have a higher body mass index, waist circumference, blood pressure and fasting glucose level, and a lower high-density lipoprotein compared to those without sarcopenia. Sarcopenia was associated with a higher shift of FRS tertile (common odds ratio, 2.67; 95% confidence interval, 1.18-6.52, P < 0.001) in males. However, this association was not significant in female survivors. CONCLUSIONS: Sarcopenia was associated with an increased CVD risk in Korean male cancer survivors. Interventions to prevent sarcopenia may be necessary to improve cardiovascular burden in cancer survivors.

Protective Effect of Genistein against Neuronal Degeneration in ApoE-/- Mice Fed a High-Fat Diet.

Altered cholesterol metabolism is believed to play a causal role in major pathophysiological changes in neurodegeneration. Several studies have demonstrated that the absence of apolipoprotein E (ApoE), a predominant apolipoprotein in the brain, leads to an increased susceptibility to neurodegeneration. Previously, we observed that genistein, a soy isoflavone, significantly alleviated apoptosis and tau hyperphosphorylation in SH-SY5Y cells. Therefore, we investigated the neuroprotective effects of dietary genistein supplementation (0.5 g/kg diet) in the cortex and hippocampus of wild-type C57BL/6 (WT) and ApoE knockout (ApoE-/-) mice fed a high-fat diet (HFD) for 24 weeks. Genistein supplementation alleviated neuroinflammation and peripheral and brain insulin resistance. Reductions in oxidative and endoplasmic reticulum stress were also observed in ApoE-/- mice fed a genistein-supplemented diet. Beta-secretase 1 and presenilin 1 mRNA levels and beta-amyloid peptide (Aß) protein levels were reduced in response to genistein supplementation in ApoE-/- mice but not in WT mice. Although the absence of ApoE did not increase tau hyperphosphorylation, genistein supplementation reduced tau hyperphosphorylation in both WT and ApoE-/- mice. Consistent with this result, we also observed that genistein alleviated activity of c-Jun N-terminal kinase and glycogen synthase kinase 3ß, which are involved in tau hyperphosphorylation. Taken together, these results demonstrate that genistein alleviated neuroinflammation, Aß deposition, and hyperphosphorylation in ApoE-/- mice fed an HFD.